1. Aetiology and current evidence base for Weight Management Naveed Sattar Professor of Metabolic Medicine BHF GCRC, University of Glasgow & Hon Consultant Glasgow Royal Infirmary

2. Outline How much obesity and where? How much obesity and where? What are the medical consequences? What are the medical consequences? Mechanisms to metabolic disease – “ectopic fat” Mechanisms to metabolic disease – “ectopic fat” Some hard truths about wt loss – Some hard truths about wt loss – “why hard to lose…..” “why hard to lose…..” What can be done about it What can be done about it

3. Rates UK, social class variations UK, social class variations Worldwide Worldwide Children Children

4. UK rates since 1980 Lean, Gruer, Alberti, Sattar (2006) BMJ epidemic

6. FORESIGHT forecast 2025 2025 40% adults obese (2 in 5) 40% adults obese (2 in 5) By 2050 – Britain a mainly obese society By 2050 – Britain a mainly obese society

8. Changing prevalence of obesity in the UK Prevalence of obesity (BMI > 30) in UK women 1994 - 2002

9. Which disease process is more closely linked to obesity?

10. 1. UKPDS Group. Diabetes Res 1990; 13: 1–11. 2. The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317. Type 2 diabetes – the microvascular burden at diagnosis a decade or so ago Erectile dysfunction 1 20% Retinopathy 1 21% Neuropathy 1 12% Nephropathy 2 18%

11. Yearly diabetes prevalence 1995-2005 Ontario Canada Lipscombe & Hux Lancet 2007

12. Summary on obesity rates On rise globally On rise globally UK – ahead in Europe UK – ahead in Europe 40% obesity in ~17 year time 40% obesity in ~17 year time Deprivation-linked Deprivation-linked Diabetes most closely associated Diabetes most closely associated T2DM in children T2DM in children Preventing Obesity is real target

13. Less well know risks of Obesity?

14. Medical Complications of Obesity Phlebitis venous stasis Coronary heart disease Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Gall bladder disease Gout Diabetes Osteoarthritis Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Hypertension Dyslipidemia Cataracts Skin Pancreatitis Idiopathic intracranial hypertension Cancer breast, uterus, cervix, prostate, kidney colon, esophagus, pancreas, liver Gynecologic abnormalities abnormal menses/ infertility polycystic ovarian syndrome Numerous pregnancy comps. Stroke

15. Populations more susceptible to adverse effects of weight gain?

16. Hot spots for type 2 diabetes IDF Atlas 2003

17. The Middle-East – world diabetes hot-spot 18.7% 16.8% 15.4% 14.6% 13.4% DM prevalence for adults age 20-79

18. Mukhopadhyay*, Forouhi*, Fisher, Kesson, Sattar. Diab Med 2005 Whites n=1557 South Asians n=210 Age at diagnosis 57 46 BMI 30 28.7

19. Chan JM et al. Diabetes Care 1994; 17: 961–969. BMI Risk of Type 2 diabetes 60 23–23.9 < 23 24–24.925–26.927–28.929–30.931–32.933–34.9 > 35 0 50 40 30 20 10 OVERWEIGHTOBESE OVERWEIGHTOBESE Weight gain pulls trigger

20. Obesity to Diabetes – concept of ectopic fat…. Or “fat in wrong places”

21. Most fat is healthy Who has most fat? Who has most fat? Women Women Less CHD? Less CHD? Less diabetes? Less diabetes? Why? Why? More Subcutaneous fat More Subcutaneous fat

22. Men vs. Women – DM riskrisk? Logue et al (In press) Diabetologia Men Women

23. ECTOPIC CONCEPT Consider 100kg man Consider 100kg man Total fat ~35kg Total fat ~35kg 70-75% will be Subcutaneous 70-75% will be Subcutaneous 10-15% Visceral fat 10-15% Visceral fat 10-15% elsewhere (E) 10-15% elsewhere (E)

24. Subcutaneous GOOD But if storage capacity exceeded Or diminished VF E (0.5-6kg) Ethnicity Genes/ Programming Illness These sites empty quicker 5% weight loss (100kg man) ~ 30% VF loss Ectopic fat Muscle and Liver Elsewhere

25. Excess calories (increased intake or reduced energy expenditure) FAT ‘Spill over’ pancreatic beta cell muscle Subcutaneous stores overwhelmed ( genes, ethnicity, ageing ) Hepatic lipid accumulation Perivascular fat  Endothelial dysfunction Insulin resistance Hyperglycaemia

26.  glucose Production (FBG) fat cells larger Fat accumulation in liver – when and what signs? LiverEnzymesALTGGT  trigs Sattar et al (2007) Diabetes Fat Glucose(protein) Fattyacids DNL oxidation Less insulin 

27. Liver fat vs. alcohol ALT > AST ALT > AST GGT high GGT high Overweight Overweight Glucose high normal Glucose high normal HDL-C often low HDL-C often low AST>ALT AST>ALT MCV high MCV high HDL-C higher than expected! HDL-C higher than expected! Not necessarily overweight or high glucose Not necessarily overweight or high glucose

28. Case MR RCN BMI 34 BMI 34 FBG 6.2 mmol/l FBG 6.2 mmol/l ALT 67 (<50) AST 34 (<50) ALT 67 (<50) AST 34 (<50) Trig 3.9 ( 1.0 mmol/l) Trig 3.9 ( 1.0 mmol/l) IF AST starts to rise >0.8 of ALT (e.g. AST 80 vs ALT 85) – then think of NASH IF AST starts to rise >0.8 of ALT (e.g. AST 80 vs ALT 85) – then think of NASH

29. Keeping liver fat down? Petersen et al Diabetes. 2005 N=8 subjects with diabetes - Hypocaloric low fat diet (3%) Wt 86 to 78 kg Glucose 8.8 to 6.6 mmol/l Insulin 174 to 66 pmol/l Percent fat 12% to ~2%

30. Research summary Diabetes unmasked by excess weight gain Diabetes unmasked by excess weight gain if family Hx DM, South Asian, at lower BMI if family Hx DM, South Asian, at lower BMI  weight leads to  ectopic fat  weight leads to  ectopic fat Ectopic fat makes organs insulin resistant Ectopic fat makes organs insulin resistant Signs of excess ‘ectopic’ liver fat common Signs of excess ‘ectopic’ liver fat common Expanding visceral fat – i.e. waist line – a marker of ‘saturated’ subcutaneous fat store Expanding visceral fat – i.e. waist line – a marker of ‘saturated’ subcutaneous fat store

31. PART 2 – treatment of obesity thoughts on prevention

32. Why are we in this mess? Foresight

33. Simple surely “Too much in, not enough out”

34. Moving on from Foresight Understanding obesity hampered by inaccurate data on energy intake and expenditure Understanding obesity hampered by inaccurate data on energy intake and expenditure –Heavier people have higher energy expenditure and intake –Almost all the increase in weight in US can be attributed to  Total Energy Intake (rather than  PA) (500kcal adults, 300kcal children)

35. Children Adults x Data from Swinburn et al 2009 Heavier people have higher energy expenditure, and thus intake

36. Implications People with lower BMIs need substantially less food energy to maintain weight People with lower BMIs need substantially less food energy to maintain weight To achieve and maintain “healthy” weight, obese individuals need big sustained reduction in energy intake or huge increases in PA To achieve and maintain “healthy” weight, obese individuals need big sustained reduction in energy intake or huge increases in PA

37. Are we lazier and greedier than prior generations? What did foresight conclude? What did foresight conclude? People in the UK are not more glutinous that previous generations, and their biology is not different People in the UK are not more glutinous that previous generations, and their biology is not different But major changes in society, work patterns, transport, food production and sales But major changes in society, work patterns, transport, food production and sales Pace of technology exceeding human evolution Pace of technology exceeding human evolution

39. “What is provided is what is eaten So what is provided has to change” Lean, Gruer, Alberti, Sattar (2006) BMJ

40. Recommended for 5-10yr olds. The label boasts virtually fat free Contains Artificial sweeteners 108 calories and 9.6g of sugar per 100g Contains 40g of sugar per 100g 174 calories per bowl Salt also is its third biggest ingredient

42. Other facts about food changes Cost of fruit & veg:  Cost of fruit & veg:  Sugar and fat cost:  Sugar and fat cost:  Overproducing food Overproducing food 80% of daily salt intake via processed foods – cereals etc 80% of daily salt intake via processed foods – cereals etc Products designed to be tastier Products designed to be tastier  Sugar, fat, salt  Sugar, fat, salt

43. 1978 Crisp packet once per week, if lucky Crisp packet once per week, if lucky Perhaps one biscuit per day, if lucky Perhaps one biscuit per day, if lucky No coke, yogurts, fast foods except chip shops No coke, yogurts, fast foods except chip shops All meals at home cooked by mum All meals at home cooked by mum Walked everywhere, played outside all time Walked everywhere, played outside all time No computer, etc No computer, etc

44. Much more complex

45. FORESIGHT The full obesity system map with thematic clusters

46. Environment  obesogenic

47. Primary driver for epidemic Overeating or under activity? Jeffery RW, Harnack LJ. Evidence Implicating Eating as a Primary Driver for the Obesity Epidemic. Diabetes 2007;56:2673-6

48. Simple considerations We all love food – even…. We all love food – even…. Food more plentiful Food more plentiful Increasing density, less time, consume fast Increasing density, less time, consume fast Sugary drinks abound Sugary drinks abound How fast can you eat 200 calories? How fast can you eat 200 calories? How fast can you burn 200 calories? How fast can you burn 200 calories? A moment on the lips…. A moment on the lips….

49. 1949 1949 “…an epidemic; under the right economic & social circumstances, obesity from overeating will be a dominant nutritional problem.” Ancel Keys

50. Government Leadership  People and the public (you and me) Public education little effect on behaviour sets the scene, increase awareness, helps support for action recognise inequalities  Public sector work (Schools, prisons, hospital )  Food industry (the Five Ps product, promotion, portion size, packaging, pricing) Re-formulations and labelling; Portions and promotions Advertising and marketing Huge Tin of Roses £4

51. Food, retail and catering Industry “Increase healthy options” “increase range of portion sizes” “promoting fruits and vegetables”

52. Food, retail and catering Industry- HALF A STORY! “Increase healthy options” “increase range of portion sizes” “promoting fruits and vegetables DECREASE LESS HEALTHY OPTIONS DECREASE LARGE PORTION SIZES DECREASE CONFECTIONERY OPTIONS At very least …?Level playing field…….

53. Reality: incredibly hard to lose AND sustain weight loss Very hard to lose weight by physical activity alone

54. “Most do not wish to be overweight” Up to half who are obese will not lose weight by any medical method Lean, Gruer, Alberti, Sattar (2006) BMJ

55. Stanley S et al. Physiol Rev 2005; 85: 1131 Appetite/satiety signals impaired when obese

56. Obesity – public health issue – prevention must be priority Limit “energy dense” foods  sat fat,  refined sugar  Fruit & Veg.   fibre…. Snacking – eat more fruit…. Chew etc Less smoothies / fruit juices

57. Treating obesity?

58. Systematic reviews - SIGN Dietary and lifestyle up to 5kg (2-4 yrs) Dietary and lifestyle up to 5kg (2-4 yrs) Drugs 5-10kg (1-2 yrs) Drugs 5-10kg (1-2 yrs) Surgery ~25-75kg (2-4 years) Surgery ~25-75kg (2-4 years)

59. 1. Cut sugary drinks – Asked how many spoonfuls of sugar in x,y, z etc Coca-Cola Red Bull Irn Bru “Healthy drinks?” Copella Apple Juice Frijj Chocolate Milk Shake Lucozade Orange Pom Wonderful Ribena Innocent Smoothie Tropicana Orange

60. Tea spoons of sugar

61. Drinks sugar content not understood People slightly overestimated the amount of sugar in carbonated drinks, BUT significantly underestimated sugar levels in – milkshake, – a smoothie, – a leading sports drink and – a variety of fruit juices – – by as much as 17 tea spoons for one fruit juice drink An example of lack of clarity / miss-selling? Paper being written up……..

63. In clinical practice? Refer to where? NHS not alone Ask – not all patients ready to discuss weight Ask – not all patients ready to discuss weight Assess – BMI still best (accuracy – more data on longer associations) Assess – BMI still best (accuracy – more data on longer associations) Advice – health service may not be best place to improve weight Advice – health service may not be best place to improve weight Susan Jebb (Foresight report) Susan Jebb (Foresight report)

64. Weight watchers beats GP practice (Jebb et al Lancet 2011 RCT, 722 patients)

65. WW - good for wider use Referral to WW with regular weighing, advice about diet and activity, motivational sessions and group support can offer early intervention for weigh management in overweight and obese that can be delivered at large scale

66. Adapted from Rössner, 1992 by U.S. Institute of Medicine, 1995. 1. Sustained weight, no increase. 2. Minor weight loss with dietary change to reduce risk of complications. 3. Weight normalisation: rare Body weight Obese Normal Years of management or intermittent monitoring Overweight Treatment strategies Successes Natural course of further weight gain. What do we tell our patients  50-100kcal per day for weight maintenance

67. Graded reductions in energy intake & effect over time

68. Retrain your taste buds gradually – goal setting 1stchange 2 nd change 3rdchange

69. Final summary Rates – epidemic – 40% by 2025 Rates – epidemic – 40% by 2025 Risks – plentiful – all body systems,  QOL Risks – plentiful – all body systems,  QOL Research – ectopic fat  many effects Research – ectopic fat  many effects Reality – prevention must be key as once obese, reversal v. hard by any medical method Reality – prevention must be key as once obese, reversal v. hard by any medical method Patients – emphasise small and sustainable changes…intake and activity…achieve and extend if needed. Patients – emphasise small and sustainable changes…intake and activity…achieve and extend if needed.